T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Prediction of late complications of femoral neck fractures by scintigraphy

Summary A prospective study was undertaken to determine the value of scintigraphy in predicting nonunion or necrosis of the femoral head following femoral neck fractures. Scintigraphy was carried out in 49 patients before operation and in 37 one week after operation; in 18 it was done before and after operation. The uptake of isotope was estimated visually as either normal or reduced compared to the opposite side. All the patients were followed up for at least 2 years. The results indicate that pre-operative bone scintigraphy is useful in elderly patients to predict nonunion and necrosis, and therefore is recommended to select those patients who will benefit from primary arthroplasty instead of fixation of the fracture.

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Résumé Etude prospective de la valeur de la scintigraphie dans la prévision des complications tardives après fracture du col du fémur. Une scintigraphie a été réalisée avant l'intervention chez 49 patients et une semaine après chez 37 autres; dans 18 cas elle a été faite avant et après l'opération. La concentration d'isotopes a été évaluée visuellement et considérée comme normale ou comme diminuée par comparaison avec la hanche opposée. Tous les patients ont été suivis deux ans au moins. Les résultats permettent de penser que la scintigraphie pré-opératoire est un examen utile chez les sujets âgés présentant une fracture du col avec déplacement pour prédire pseudarthrose et nécrose de la tête fémorale. Elle permet de choisir les patients pour lesquels l'arthroplastie est préférable à l'ostéosynthèse.

     

Myocardial sestamibi single-photon emission tomography: Variations in reference values with gender, age and rest versus stress?

Reference data files support the evaluation of myocardial perfusion single-photon emission tomography (SPET). The aim of this study was to create a large reference data base for technetium-99m sestamibi SPET, age and gender matched to the general patient population. One hundred and twenty-eight healthy volunteers (76 males and 52 females) with a likelihood of coronary artery disease of less than 5% underwent rest and maximal exercise^99mTc-sestamibi SPET with a 2-day protocol and 180° elliptical rotation. The normalized activity values of^99mTc-sestamibi in the inferior wall differed significantly between men and women. Age variations were found for men in the anterior wall. Normalized activity values in all four walls were strikingly similar during rest and stress. Our results suggest that the use of reference files in^99mTc-sestamibi SPET requires a gender- and, for males, possibly an age-matched reference population. Different reference files at rest and during stress might not be necessary.     

Corticosteroids for multiple sclerosis: II. Application for disease-modifying effects

Physicians who treat multiple sclerosis (MS) face the challenge of patients exhibiting ongoing disease activity, including exacerbations, loss of functional capabilities, intellectual decline, and radiologic progression, despite being on a disease-modifying agent (DMA). After searching for factors that might at least in part explain these changes—such as nonadherent drug-taking behavior, or the presence of interfer-on-neutralizing antibodies—some providers may ultimately decide to switch the patient to another DMA. In most circumstances, patients likely derive only partial effects from these agents, even in the absence of compromising factors. Thus, a number of factors must be considered in order to intensify the treatment regimen in response to disease progression. In the context of an inadequate treatment response to a DMA, some clinicians will convert the patient to an alternative therapy, and others will instead use a second agent in combination with the first (the so-called platform agent). In the first of this two-part series, we explored the use of anti-inflammatory CS and ACTH to treat MS exacerbations. Although we underscored the limited availability of evidence-based studies to support specific regimens for this purpose, there is an even greater paucity of data to support the routine use of these agents in order to achieve chronic disease-modifying effects in those who continue to deteriorate clinically, radiographically, or both. Without doubt, a number of factors influence the formulation of combination treatment plan for MS. Nevertheless, we will focus on the rationale and practical schemes that can be considered for using corticosteroids (CS) (and perhaps even ACTH) in an attempt to modify various domains of ongoing disease activity.     

Entwicklung der Hornhautdicke und -endothelzelldichte nach Kataraktextraktion mittels Phakoemulsifikation

Ziel der vorliegenden Untersuchung war es, das Ausma? der Hornhautsch?digung durch eine Kataraktextraktion im Hinblick auf das Hornhautendothel und die Hornhautdicke zu untersuchen. Patienten und Methode: In einer prospektiven Untersuchung wurde die Entwicklung der Hornhautdicke und der Endothelzelldichte an 48 Patienten untersucht. Die Patienten wurden mittels Phakoemulsifikation operiert. Die Hornhautdicke wurde dabei mit einem Ultraschallpachymeter bei 12 Uhr und im Hornhautzentrum und die Endothelzelldichte mit einer Endothelzellkamera an den gleichen Me?punkten pr?operativ sowie 4 Wochen, 4 Monate und 1 Jahr postoperativ bestimmt. Ergebnisse: Ein Jahr postoperativ nahm die Hornhautdicke nach Phakoemulsifikation an der 12-Uhr-Position um ca. 9% und im Hornhautzentrum um ca. 12% im Vergleich zum pr?operativen Wert zu. Die Endothelzelldichte war 1 Jahr postoperativ an der 12-Uhr-Position um ca. 27% und im Zentrum um ca. 18% reduziert. Das Patientenalter korrelierte signifikant mit dem Zellverlust an beiden Me?punkten. Bezüglich der Dickenzunahme ist keine signifikante Korrelation festzustellen. Schlu?folgerung: Nach einer Kataraktextraktion ist der Hornhautstoffwechsel reduziert. Als Indikator k?nnen der Verlauf der Endothelzelldichte und der Dicke herangezogen werden.      

Tuberculosis in healthcare workers caring for a congenitally infected infant.

OBJECTIVE: To assess the extent of nosocomial transmission of tuberculosis among infants, family members, and healthcare workers (HCWs) who were exposed to a 29-week-old premature infant with congenital tuberculosis, diagnosed at 102 days of age. DESIGN: A prospective exposure investigation using tuberculin skin test (IST conversion was conducted. Contacts underwent two skin tests 10 to 12 weeks apart. Clinical examination and chest radiographs were performed to rule out disease. Isoniazid prophylaxis was administered to exposed infants at higher risk. SETTING: A neonatal intensive care unit in an urban hospital in Brussels, Belgium. PARTICIPANTS: Ninety-seven infants, 139 HCWs, and 180 visitors. RESULTS: Newly positive TST results occurred in HCWs who had been in close contact with the infant. Six (19%) of 32 primary care nurses and physicians had TST conversions and received treatment. Among the 97 exposed infants, 85 were screened and 34 were identified as at higher risk of infection. Of these, 27 received preventive isoniazid. None of the infants and none of the 93 other infants' family members evaluated were infected. CONCLUSIONS: Congenital tuberculosis in an infant poses a risk for nosocomial transmission to HCWs. Delayed diagnosis of this rare disease and close proximity are the most important factors related to transmission.